The invention generally relates to suramin and its derivatives in topical formulations and their use as microbicidal contraceptives for the prevention of sexually transmitted diseases (STD) and conception. According to the present invention, it has been found herein that suramin and its derivatives display potent activity against STD pathogens and has displayed antisperm activity, and alone or in combination with other sperm-function inhibitors, including spermicides, and/or other antimicrobials, including antivirals, they constitute effective vaginal contraceptive microbicides.
The increasing prevalence of STD is a serious public health problem affecting both developed and less-developed countries. In the latter, the acquired immune deficiency syndrome (AIDS) epidemic is taking a devastating toll in human lives. Constrained by lack of money, overpopulation and cultural habits that make condoms unpopular, these countries see a dramatic increase in the number of human immunodeficiency virus (HIV)-infected people, in some cases reaching one third of the population of reproductive age. There is an urgent need to develop safe, prophylactic, female-controlled agents that are effective against sexually transmitted pathogens, particularly HIV, and conception.
Nonoxynol-9 (N-9), a nonionic surfactant, is the only FDA-approved spermicide currently in the U.S. market. Other surfactants, such as benzalkonium chloride, are available as part of spermicidal preparations in Canada and Europe. Due to their effects on lipids, these surfactants display anti-HIV activity in vitro, disrupting the viral envelope and inactivating the virus. Unfortunately, as it has clearly been demonstrated for N-9, these surfactants alone do not appear to confer significant protection in vivo. Several clinical trials with N-9 have shown lack of reduction in the incidence of HIV infection (Rowe, Lancet., 349: 1074 1997; Hira et al., Int J. STD AIDS., 8(4) 243-50 1997; Martin et al., Sex. Transm. Dis., 24(5): 279-283, 1997; Roddy et al., N. Engl. J. Med., 339(8): 504-10 1998; Van Damme et al., Lancet., 360(9338): 971-7 2002). In fact, it has been demonstrated that N-9 actually increases the risk of genital inflammation (Stafford et al., J. Acquir Immune Defic Syndr. Hum. Retrovirol. 17(4): 327-31 1998), urinary tract infections (Fihn et al., Am. J. Epidemiol, 144(5): 512-20 1996), vulvovaginal candidiasis (Geiger and Foxman, Epidemiology., 7(2): 182-7 1996) and genital ulcers (Feldblum, Genitourin Med., 72(6): 451-2 1996). A recent study (Fichorova et al., J. Infect. Dis., 184(4): 418-28 2001) reveals that N-9 is cytotoxic for the vaginal epithelium and induces the release of proinflammatory cytokines which, in turn, recruit immune cells that are targets for HIV, thus facilitating its tissue invasion.
For these reasons, there is a continuing need to develop a topical formulation that is harmless to mucosae and the mucosal microflora, effective against HIV and other STD pathogens such as Herpes simplex virus (HSV), Cytomegalovirus (CMV), Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT), and at the same time, offers contraceptive protection.